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Abstract

Silicon, an element, has been reported to possess various osteogenic biological functions. However, the precise cellular action mechanism of silicon in osteogenesis is elusive. Here, we examine whether autophagy is associated with the osteogenic differentiation and mineralization of preosteoblasts stimulated by orthosilicic acid (unique soluble form of silicon). The autophagy induced by silicon was detected via autophagy-related protein expression. The correlation between orthosilicic acid-induced autophagy and the osteogenic process was verified by the autophagy inhibitor 3-methyladenine. We also investigated its applicability in vivo through bone mineral density, collagen staining, hydroxyproline, and immunohistochemistry on osteoporosis rats. Concentrations above 10 µM increased alkaline phosphatase activity, whereas those up to 50 µM decreased alkaline phosphatase activity. Orthosilicic acid at concentrations up to 20 µM increased the osteogenetic indicators, the expression of the autophagy-related factors SQSTM1/p62, and the conversion of microtubule-associated protein 1 light chain 3-II (LC3-II) from microtubule-associated protein 1 light chain 3-I (LC3-I) according to Western Blot analyses. The application of 3-methyladenine decreased the expression of Runt-related transcription factor 2 (RUNX-2), bone morphogenetic protein-2, and collagen I in the Western Blot analysis. Low dose of orthosilicic acid supplemented rats (OVX-1, 2) showed improvements in such parameters as the expression rate of collagenous fiber in bone, bone mineral density, femoral hydroxyproline content, and bone morphogenetic protein-2; while high dose groups (OVX-3, 4) presented no better outcome. The present study showed that orthosilicic acid stimulated the osteogenic differentiation and mineralization of cultured preosteoblasts by inducing autophagy. In addition, it also can enhance bone mineral density of osteoporosis rats.

Keywords

Osteoporosis orthosilicic acid osteogenesis autophagy bone mineral density

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References

Lane

NE.

Epidemiology, etiology, and diagnosis of osteoporosis. Am J Obstet Gynecol 2006; 194: S3–S11.

Ikeda

Takeshita

Factors and mechanisms involved in the coupling from bone resorption to formation: how osteoclasts talk to osteoblasts. J Bone Metab 2014; 21: 163–167.

Sahin

Onderci

Sahin

et al . Dietary arginine silicate inositol complex improves bone mineralization in quail. Poult Sci 2006; 85: 486–492.

Spector

Calomme

Anderson

et al . Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial. BMC Musculoskelet Disord 2008; 9: 85.

Calomme

Geusens

Demeester

et al . Partial prevention of long-term femoral bone loss in aged ovariectomized rats supplemented with choline-stabilized orthosilicic acid. Calcif Tissue Int 2006; 78: 227–232.

Liu

Fang

Yuan

et al . Suppression of autophagy by FIP200 deletion leads to osteopenia in mice through the inhibition of osteoblast terminal differentiation. J Bone Miner Res 2013; 28: 2414–2430.

Onal

Piemontese

Xiong

et al . Suppression of autophagy in osteocytes mimics skeletal aging. J Biol Chem 2013; 288: 17432–17440.

Wang

Wan

Shao

et al . Notoginsenoside R1 stimulates osteogenic function in primary osteoblasts via estrogen receptor signaling. Biochem Biophys Res Commun 2015; 466: 232–239.

da Silva

Spinelli

Rodrigues

SV.

Fast and sensitive collagen quantification by alkaline hydrolysis/hydroxyproline assay. Food Chem 2015; 173: 619–623.

10.

Sroga

Vashishth

UPLC methodology for identification and quantitation of naturally fluorescent crosslinks in proteins: a study of bone collagen. J Chromatogr B Analyt Technol Biomed Life Sci 2011; 879: 379–385.

11.

Acil

Springer

Niehoff

et al . Proof of direct radiogenic destruction of collagen in vitro. Strahlenther Onkol 2007; 183: 374–379.

12.

Zheng

Wang

et al . Plasma interleukin 33 level in patients with osteonecrosis of femoral head: an alarmin for osteonecrosis of the femoral head? J Investig Med 2014; 62: 635–637.

13.

Zheng

Wang

et al . The association of eNOS gene polymorphism with avascular necrosis of femoral head. PLoS One 2014; 9: e87583.

14.

Hocking

Whitehouse

Helfrich

MH.

Autophagy: a new player in skeletal maintenance?

J Bone Miner Res 2012; 27: 1439–1447.

15.

Ferreira

Porter

Wehling

et al . Inflammatory cytokines induce a unique mineralizing phenotype in mesenchymal stem cells derived from human bone marrow. J Biol Chem 2013; 288: 29494–29505.

16.

Thomas

Puleo

DA.

Infection, inflammation, and bone regeneration: a paradoxical relationship. J Dent Res 2011; 90: 1052–1061.

17.

Bae

Kim

Choi

et al . Short-term administration of water-soluble silicon improves mineral density of the femur and tibia in ovariectomized rats. Biol Trace Elem Res 2008; 124: 157–163.

18.

Sripanyakorn

Jugdaohsingh

Dissayabutr

et al . The comparative absorption of silicon from different foods and food supplements. Br J Nutr 2009; 102: 825–834.

19.

Komori

Regulation of osteoblast differentiation by transcription factors. J Cell Biochem 2006; 99: 1233–1239.

20.

Chin

Yang

Chai

et al . Effects of medicinal herb Salvia miltiorrhiza on osteoblastic cells in vitro. J Orthop Res 2011; 29: 1059–1063.

21.

Trivedi

Kumar

et al . Kaempferol has osteogenic effect in ovariectomized adult Sprague-Dawley rats. Mol Cell Endocrinol 2008; 289: 85–93.

22.

Yang

Meng

Yang

Autophagy protects osteoblasts from advanced glycation end products-induced apoptosis through intracellular reactive oxygen species. J Mol Endocrinol 2016; 56: 291–300.

23.

Mizushima

Yoshimori

Levine

Methods in mammalian autophagy research. Cell 2010; 140: 313–326.

24.

Yang

Zheng

et al . Oxidative damage to osteoblasts can be alleviated by early autophagy through the endoplasmic reticulum stress pathway–implications for the treatment of osteoporosis. Free Radic Biol Med 2014; 77: 10–20. [Mismatch]

25.

Chagin

AS.

Effectors of mTOR-autophagy pathway: targeting cancer, affecting the skeleton. Curr Opin Pharmacol 2016; 28: 1–7.

26.

Luo D, Ren H, Li T, Lian K, et al. Rapamycin reduces severity of senile osteoporosis by activating osteocyte autophagy. Osteoporos Int 2016 27: 1093–1101.

27.

Chen K, Yang YH, Jiang SD, et al. Decreased activity of osteocyte autophagy with aging may contribute to the bone loss in senile population. Histochem Cell Biol 2014; 142: 285–295.

28.

Yang GE, Duan X, Lin D, et al. Rapamycin-induced autophagy activity promotes bone fracture healing in rats. Exp Ther Med 2015; 10: 1327–1333.

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The role of orthosilicic acid-induced autophagy on promoting differentiation and mineralization of osteoblastic cells

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